Dioscin pretreatment ameliorates ferroptosis in cardiomyocytes after myocardial infarction via inhibiting endoplasmic reticulum stress

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 29, 2025

Language: Английский

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Cardioprotective potential of vanillic acid

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2022, Volume and Issue: 50(3), P. 193 - 204

Published: Nov. 12, 2022

Nowadays, cardiovascular diseases (CVDs) are a global threat to public health, accounting for almost one-third of all deaths worldwide. One the key mechanistic pathways contributing development CVDs, including cardiotoxicity (CTX) and myocardial ischaemia-reperfusion injury (MIRI) is oxidative stress (OS). Increased generation reactive oxygen species (ROS) closely associated with decreased antioxidant capacity mitochondrial dysfunction. Currently, despite availability modern pharmaceuticals, dietary-derived antioxidants becoming more popular in developed societies delay progression CVDs. derived from herbs, fruits, whole grains, juices, beers, wines vanillic acid (VA), which, as phenolic compound, possesses different therapeutic properties, cardioprotective. Based on experimental evidence, VA improves function result reduction ROS production, aggravates antioxidative status, scavenges free radicals, reduces levels lipid peroxidation, thereby decreasing cardiac dysfunction, particular CTX MIRI. Considering role OS pathophysiology purpose this study comprehensively address recent evidence importance system.

Language: Английский

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SIRT3 attenuates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome via autophagy

Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 207, P. 115354 - 115354

Published: Nov. 24, 2022

Language: Английский

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Tumor Necrosis Factor Family Members and Myocardial Ischemia-Reperfusion Injury: State of the Art and Therapeutic Implications

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4606 - 4606

Published: Feb. 27, 2023

Ischemic heart disease is the principal cause of death worldwide and clinically manifests as myocardial infarction (MI), stable angina, ischemic cardiomyopathy. Myocardial defined an irreversible injury due to severe prolonged ischemia inducing cell death. Revascularization helpful in reducing loss contractile myocardium improving clinical outcome. Reperfusion rescues from but also induces additional called ischemia-reperfusion injury. Multiple mechanisms are involved injury, such oxidative stress, intracellular calcium overload, apoptosis, necroptosis, pyroptosis, inflammation. Various members tumor necrosis factor family play a key role In this article, TNFα, CD95L/CD95, TRAIL, RANK/RANKL/OPG axis regulation tissue damage reviewed together with their potential use therapeutic target.

Language: Английский

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Discovery of a novel 1,3,4-oxadiazol-2-one-based NLRP3 inhibitor as a pharmacological agent to mitigate cardiac and metabolic complications in an experimental model of diet-induced metaflammation

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 257, P. 115542 - 115542

Published: June 3, 2023

Inspired by the recent advancements in understanding binding mode of sulfonylurea-based NLRP3 inhibitors to sensor protein, we developed new replacing central sulfonylurea moiety with different heterocycles. Computational studies evidenced that some designed compounds were able maintain important interaction within NACHT domain target protein similarly most active inhibitors. Among studied compounds, 1,3,4-oxadiazol-2-one derivative 5 (INF200) showed promising results being prevent NLRP3-dependent pyroptosis triggered LPS/ATP and LPS/MSU 66.3 ± 6.6% 61.6 11.5% reduce IL-1β release (35.5 8.8% μM) at 10 μM human macrophages. The selected compound INF200 (20 mg/kg/day) was then tested an vivo rat model high-fat diet (HFD)-induced metaflammation evaluate its beneficial cardiometabolic effects. significantly counteracted HFD-dependent "anthropometric" changes, improved glucose lipid profiles, attenuated systemic inflammation biomarkers cardiac dysfunction (particularly BNP). Hemodynamic evaluation on Langendorff indicate limited myocardial damage-dependent ischemia/reperfusion injury (IRI) improving post-ischemic systolic recovery attenuating contracture, infarct size, LDH release, thus reversing exacerbation obesity-associated damage. Mechanistically, hearts, IFN200 reduced IRI-dependent activation, inflammation, oxidative stress. These highlight potential novel inhibitor, INF200, ability reverse unfavorable cardio-metabolic associated obesity.

Language: Английский

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Fractalkine Signalling (CX3CL1/CX3CR1 Axis) as an Emerging Target in Coronary Artery Disease

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(14), P. 4821 - 4821

Published: July 21, 2023

Acute myocardial infarction (MI) is the most common and dramatic complication of atherosclerosis, which, despite successful reperfusion therapy, can lead to incident heart failure (HF). HF occurs when healing process impaired due adverse left ventricular remodelling, be result so-called ischaemia/reperfusion injury (IRI), visualised by development intramyocardial haemorrhage (IMH) or microvascular obstruction (MVO) in cardiac MRI. Thus far, translation novel pharmacological strategies from preclinical studies target either IRI post MI have been largely unsuccessful. Anti-inflammatory therapies also carry risk affecting immune system. Fractalkine (FKN, CX3CL1) a unique chemokine, present as transmembrane protein on endothelium, following cleavage soluble ligand, attracting leukocyte subsets expressing corresponding receptor CX3CR1. We shown previously that fractalkine CX3CR1 associated with MVO patients undergoing primary PCI. Moreover, inhibition an allosteric small molecule antagonist (KAND567) rat model reduces acute infarct size, inflammation, IMH. Here we review cellular biology its receptor, along ongoing introduce future coronary artery disease, specifically infarction.

Language: Английский

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The Protective Role of Molecular Hydrogen in Ischemia/Reperfusion Injury

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7884 - 7884

Published: July 18, 2024

Ischemia/reperfusion injury (IRI) represents a significant contributor to morbidity and mortality associated with various clinical conditions, including acute coronary syndrome, stroke, organ transplantation. During ischemia, profound hypoxic insult develops, resulting in cellular dysfunction tissue damage. Paradoxically, reperfusion can exacerbate this through the generation of reactive oxygen species induction inflammatory cascades. The extensive sequelae IRI necessitate development therapeutic strategies mitigate its deleterious effects. This has become cornerstone ongoing research efforts both basic translational science. review examines use molecular hydrogen for different organs explores underlying mechanisms action. Molecular is selective antioxidant anti-inflammatory, cytoprotective, signal-modulatory properties. It been shown be effective at mitigating models, heart failure, cerebral transplantation, surgical interventions. Hydrogen reduces via mechanisms, like suppression oxidative stress inflammation, enhancement ATP production, decreasing calcium overload, regulating cell death, etc. Further still needed integrate into practice.

Language: Английский

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Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8300 - 8300

Published: July 27, 2022

Given the abundance of heme proteins (cytochromes) in mitochondrion, it is evident that a meticulously orchestrated iron metabolism essential for cardiac health. Here, we examined functional significance myocardial ferritin heavy chain (FtH) model acute infarction. We report FtH deletion did not alter either mitochondrial regulatory and surveillance pathways (fission fusion) or bioenergetics response to injury. Furthermore, affect function, assessed by measurement left ventricular ejection fraction, on days 1, 7, 21 post To identify modulated providing cardiomyocyte protection coincident with deletion, performed unbiased transcriptomic analysis. found following injury, was associated upregulation several genes anti-ferroptotic properties, including oxygenase-1 (HO-1) cystine/glutamate anti-porter (Slc7a11). These results suggested HO-1 overexpression mitigates ferroptosis via Slc7a11. Indeed, using transgenic mice overexpression, demonstrate overexpressed coupled increased Slc7a11 expression. In conclusion, leads compensatory number genes, HO-1. Such induction protects heart against ischemia-reperfusion-mediated ferroptosis, preserves overall function myocardium.

Language: Английский

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Mitochondria-associated endoplasmic reticulum membranes (MAMs): Possible therapeutic targets in heart failure

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Jan. 26, 2023

Mitochondria-associated endoplasmic reticulum membranes (MAMs) are formed by physical connections of the and mitochondria. Over past decades, great breakthroughs have been made in study ER-mitochondria communications. It has identified that MAM compartments pivotal regulating neurological function. Accumulating studies indicated MAMs participate development cardiovascular diseases. However, specific role heart failure remains to be fully understood. In this article, we first summarize structural functional properties MAM-associated proteins. We then focus on roles myocardial infarction, cardiomyopathy failure, discuss involvement disease progression treatment. Elucidating these issues may provide important insights into therapeutic intervention failure.

Language: Английский

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Myocardial injury: where inflammation and autophagy meet

Burns & Trauma, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 1, 2023

Abstract Autophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles, aged proteins and intracellular contents to maintain the homeostasis of microenvironment. Activation autophagy can be observed during myocardial injury, which inflammatory responses are strongly triggered. inhibit response regulate microenvironment by removing invading pathogens mitochondria. In addition, may enhance clearance apoptotic necrotic cells promote repair tissue. this paper, we briefly review role in different cell types injury discuss molecular regulating series conditions, including ischemia, ischemia/reperfusion sepsis cardiomyopathy.

Language: Английский

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